Colposcopic appearance of cervical intraepithelial neoplasia is age dependent.

OBJECTIVE: We investigated to determine whether colposcopic, histologic, and virologic parameters of cervical intraepithelial neoplasia are influenced by a patient's age. STUDY DESIGN: A cohort of 967 women with a mean age of 37.1 years underwent screening for detection of cervical intraepithelial neoplasia by colposcopy, cytologic examination, and testing for high-risk human papillomaviruses with the Hybrid Capture System (Digene, Silver Springs, Md) and a general primer and type-specific primer polymerase chain reaction system. Cervicography was used for documentation and reproducible evaluation of the colposcopic appearance of the cervix. In 86% of patients with trivial colposcopic changes of doubtful significance (100/116) and 89% of patients with colposcopic changes consistent with cervical intraepithelial neoplasia (89/99), punch biopsy specimens were taken for histologic evaluation. RESULTS: In patients with trivial colposcopic changes of doubtful significance, histologically confirmed cervical intraepithelial neoplasia was almost as frequent (32%, 37/116) as in patients with colposcopic changes consistent with cervical intraepithelial neoplasia (43%, 43/99, difference not significant). The ratio between colposcopic evidence of cervical intraepithelial neoplasia and trivial colposcopic changes was 1.9 in patients <35 years old with cervical intraepithelial neoplasia, versus 0.5 in patients >/=35 years old with cervical intra-epithelial neoplasia (P =.005). Patients with trivial colposcopic changes of doubtful significance were older (median age 36 years) than were patients with colposcopic changes consistent with cervical intraepithelial neoplasia (median age 29 years, P =. 008). In patients with cervical intraepithelial neoplasia who had no or trivial colposcopic changes, the thickness of neoplastic epithelium was smaller (P =.008) and the number of cellular layers was lower (P =.01) than in patients with cervical intraepithelial neoplasia who had colposcopic changes consistent with cervical intraepithelial neoplasia. In patients <35 years old the rate of positive results for a high-risk human papillomavirus (P <.005) and the viral load (difference not significant) were higher than in women >/=35 years old. The rate of positive results for high-risk human papillomaviruses differed independently of age among patients with normal colposcopic findings, patients with trivial colposcopic changes of doubtful significance, and patients with colposcopic changes consistent with cervical intraepithelial neoplasia (P <.005). CONCLUSIONS: In women >/=35 years old cervical lesions associated with intraepithelial neoplasia are thinner and thus less colposcopically conspicuous than those in women <35 years old. Patients >/=35 years old with acetowhite cervical lesions consistent with trivial changes of doubtful significance should therefore undergo punch biopsy for histologic evaluation.

Human papillomavirus distribution in cervical tissues of different morphology as determined by hybrid capture assay and PCR.

Distribution of various types of genital human Papillomavirus (HPV) in smears from histologically classified cervical lesions was determined by hybrid capture assay (HCA) and was compared with a polymerase chain reaction (PCR) system using general primers (GP) in first and type specific primers (TS) in a second step. The overall agreement of high-risk HPV by HCA and the more sensitive GP/TS PCR was 80.6% (204 of 253, kappa value 0.6). Human Papillomavirus frequency by GP/TS PCR was 14-20% higher compared with HCA (p = 0.02-0.004) independent of morphology. Only one sample was positive by HCA and negative by GP/TS PCR. A significantly higher frequency was found using HCA and GP/TS PCR in smears from histologically proven cervical intraepithelial lesions (CIN) II/III compared with CIN I, tissues with minimal changes (metaplasia, cervicitis, or lack of glycogenization), or normal morphology (61% and 81% vs 8-15% and 24-34%, p < or = 0.001). Semi-quantitative estimate of HPV DNA copies by GP-PCR coincided with estimated virus load by quantitative HCA and was significantly higher in patients with CIN II/III compared with CIN I (p < 0.001). Thus, the GP-PCR may be used to monitor the amount of HPV DNA copies in clinical samples. A direct correlation between morphologic changes and HPV detection as well as virus load was found by HCA and the more sensitive GP/TS PCR.

Different detectability of high-risk HPV in smears from incident and prevalent high-grade squamous intraepithelial lesions of the cervix.

Human papillomavirus (HPV) status in cervical smears from cervical intraepithelial neoplasia (CIN) 2/3 diagnosed in 36 of 892 women with a history of normal cytology and colposcopy (incident CIN 2/3) was compared with CIN 2/3 in 40 patients with a history of abnormal cytology (prevalent CIN 2/3). In all patients cervical smears for HPV testing and cytology and two cervigrams were taken. The scrapes were collected in hybrid capture assay solution and analyzed with the hybrid capture and general primer/type-specific primer polymerase chain reaction system (GP/TS-PCR) after DNA extraction. Patients with incident and prevalent CIN 2/3 were similar with respect to age. By GP/TS-PCR carried out under suboptimal conditions due to DNA extraction, HPV DNA was detected in 69.4% (25 of 36) of smears from incident CIN 2/3 compared to 95% (38 of 40) in prevalent CIN 2/3 (P = 0.003). Using hybrid capture, smears of incident CIN 2/3 were HPV positive in 50% (18 of 36) compared to 80% (32 of 40) in prevalent CIN 2/3 (P = 0.006). High-risk HPVs were significantly less common in smears from incident CIN 2/3 compared with prevalent CIN 2/3: 36.1% vs 72.5% by GP/TS-PCR (P = 0.001) and 47.2% vs 80% by hybrid capture assay (P = 0.003), respectively. Virus load in HPV-positive smears of prevalent CIN 2/3 was significantly higher than of incident CIN 2/3 using semiquantitative PCR (P = 0.0005). Thus, high-risk HPV types were detected less frequently and in lower concentration in smears from incident CIN 2/3 than in smears from prevalent CIN 2/3.

[MSA--a new sensitive tumor marker in breast carcinoma]. / MSA--ein neuer sensitiver Tumormarker beim Mammakarzinom.

Mammary serum antigen (MSA) serum levels were evaluated for its association with histopathologic outcome of breast biopsies. 212 women were undergoing a diagnostic extirpation for suspicious lesions of the breast. Invasive breast cancer was found in 24.5%, in-situ-carcinomas in 7.1% respectively. 56.1% of the women were diagnosed with proliferating benign breast diseases and normal breast tissue was found in 12.3% of the patients. In all women pretherapeutic MSA-serum levels were measured by Inhibition-ELISA using the monoclonal antibody 3E1.2. The positivity-rates of MSA, CA15-3, TPA and CEA were compared separately and in combination. MSA was positive in 25% of breast cancer patients when a cut-off level of 55 U/ml was applied. The addition of CA15-3, TPA or CEA increased the sensitivity to 42.3% and the increment of the positivity-rate was smaller by addition of CA15-3, when compared with TPA or CEA. The highest MSA serum levels and positivity-rates were associated with malignant tumours, but there was no significant difference compared with benign epithelial proliferations (19.5% positivity rate). The lowest positivity-rate was detected in mesenchymal proliferations of the breast (4.8%, p = 0.02). To sum up one can say that MSA serum levels do not allow to discriminate benign from malignant breast diseases and MSA is 2.5 to 3 times more sensitive for the prediction of early stages breast cancer compared to CA15-3, TPA and CEA.

[The iodine status in the puerperium and in newborn infants]. / Zur Iodversorgung bei Wöchnerinnen und ihren Neugeborenen.

In this paper we report about the actual supply of iodine of women in childbred determining iodine levels in serum and milk of the mothers. No significant differences were found between women without, with treated or with untreated goitre. In early childbred and 4 weeks after birth the iodine in milk amounts to about the half of the maternal serum level and does not further increase with continuation of nursing.

[The pharmacokinetics of magnesium sulfate in pregnant women with threatened abortion and fetal retardation]. / Untersuchungen zur Pharmakokinetik von Magnesiumsulfat bei Schwangeren mit drohender Frühgeburt und fetaler Retardierung.

A contribution concerning distribution and elimination of magnesium sulphate in pregnant women with preterm labour and fetal retardation is given. From the kinetic parameters calculated a dosage regimen is recommended. To describe the physiologic magnesium level in plasma by a two-compartment model a kind of "continuous infusion" was assumed.

Effects of an intranasally administered low dose progestogen on the pituitary and gonadal functions.

This study was undertaken to investigate possible mechanisms of action of a daily intranasally administered low dose of norethisterone acetate (40 microgram) in regularly menstruating young women. Besides measurement of basal body temperature, serum concentrations of FSH, LH, estradiol and progesterone were determined over one treatment cycle. An endometrial biopsy was taken on day 27 or 28 of the cycle. In spite of a considerable individual variation in the respective values the following effects could be observed: In 8 of 9 subjects the midcycle LH peak was abolished, while basal FSH and LH levels remained within the control range of the follicular and luteal phases. A variable reduction of progesterone levels below the range indicative of a normal luteal phase function suggested a tendency to atypical corpus luteum formation. In 8 of 9 endometrial biopsies, however, secretory transformation could be found.

Transcortin as an indicator of estrogenic potency in oral contraceptives.

Serum cortisol-binding globulin (CBG) was measured before, during and following a 21-day application period of 5 oral contraceptives used in the GDR. In a second group of patients determinations were carried out at the end of a 24-month treatment period and the end of the first post-treatment cycle. From a third group of volunteers blood samples were taken at the end of the first, second and third treatment cycles. All the drugs tested produced a marked increase of CBG in serum, reaching its maximum at the end of the second treatment cycle. Within four weeks following termination of application the level fell to the control range. There were no significant differences between the various contraceptives.